Albertine Donker

General Discussion 325 9 references ranges for children of all age groups and of different origins that can be used worldwide, since the starting point of diagnosing iron disorders, such as IRIDA, is the determination of a serum hepcidin level. Third, we argue for a broader application of NGS with the aim of expanding our knowledge on the genotypic and phenotypic spectrum of the rare anemias addressed in this work. Next steps regarding the research on IRIDA involve the further elucidation of the genetic and molecular background of this disorder by performing WES sequencing of candidate genes in patients with a mono-allelic TMPRSS6 defect, and by studies that further confirm or contradict possible other cleavage targets in the BMP-SMAD hepcidin regulatory pathway of MT2. Furthermore, the clinical consequences of ID on the function of the various iron-demanding organ systems such as the muscular system (especially the heart), the thyroid gland and the brain need longitudinal assessment in IRIDA patients. In addition, there is an unmet need for biomarkers to assess functional consequences of iron deficiency beyond anemia. This will help to further elucidate the pathophysiology of IRIDA and to guide decisions on the application of different treatment modalities and dosing schemes tailored to a specific patient. The ultimate aim to achieve is the establishment of an evidence-based guideline, based on the molecular, genetic and clinical information gathered in internationally collaborating biobanks, allowing a tailored diagnosis and treatment of the individual IRIDA patient of all ages. This will limit the injury induced by both iron deficit and iron excess to a variety of organ systems, preventing the patients from lifelong sequelae that might have a considerable impact on quality of life and longevity. “Sola dosis facit venenum” (“Only the dose makes the poison”) Paracelsus (1493-1541)